HLA-I-restricted CD8⁺ T cell immunity may accelerate tumorigenesis in conjunction with VHL inactivation.

ABSTRACT: CD8⁺ T cells recognize and kill tumor cells with HLA-I tumor antigens in early tumorigenesis, the efficiency of which differs according to antigen-recognition coverage, as shown in earlier tumor onset in HLA-I homozygosity. However, the universality of these associations remains unknown. Here, we assessed the tumor type and driver mutation specificity in the association between tumor onset age and HLA-I zygosity. Statistical analyses identified an unexpected negative relationship in tumors with VHL biallelic loss, wherein HLA-I heterozygosity was associated with earlier tumor onset, while all others showed either no or a positive association. Testing on an independent dataset reproduced the VHL-dependent acceleration of tumor onset in the HLA-I heterozygous group, confirming the

SUBMITTER: Park B 

PROVIDER: S-EPMC9167969 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature